Abstract

Background

The structural and functional complexity of the mammalian central nervous system (CNS)
is organized and modified by complicated molecular signaling processes that are poorly
understood.

Results

We measured transcripts of 16,896 genes in 5 CNS regions from cohorts of young, middle-aged
and old male and female mice that had been maintained on either a control diet or
a low energy diet known to retard aging. Each CNS region (cerebral cortex, hippocampus,
striatum, cerebellum and spinal cord) possessed its own unique transcriptome fingerprint
that was independent of age, gender and energy intake. Less than 10% of genes were
significantly affected by age, diet or gender, with most of these changes occurring
between middle and old age. The transcriptome of the spinal cord was the most responsive
to age, diet and gender, while the striatal transcriptome was the least responsive.
Gender and energy restriction had particularly robust influences on the hippocampal
transcriptome of middle-aged mice. Prominent functional groups of age- and energy-sensitive
genes were those encoding proteins involved in DNA damage responses (Werner and telomere-associated
proteins), mitochondrial and proteasome functions, cell fate determination (Wnt and
Notch signaling) and synaptic vesicle trafficking.

Conclusion

Mouse CNS transcriptomes responded to age, energy intake and gender in a regionally
distinctive manner. The systematic transcriptome dataset also provides a window into
mechanisms of age-, diet- and sex-related CNS plasticity and vulnerability.